Use of spatiotemporal response behavior in sensor arrays to detect analytes in fluids

ABSTRACT

Methods, systems and sensor arrays are provided implementing techniques for detecting an analyte in a fluid. The techniques include providing a sensor array including at least a first sensor and a second sensor in an arrangement having a defined fluid flow path, exposing the sensor array to a fluid including an analyte by introducing the fluid along the fluid flow path, measuring a response for the first sensor and the second sensor, and detecting the presence of the analyte in the fluid based on a spatio-temporal difference between the responses for the first and second sensors.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a divisional of and claims priority to U.S.application Ser. No. 09/568,784, filed May 10, 2000, which claims thebenefit of Provisional Application No. 60/133,318, filed May 10, 1999and Provisional Application No. 60/140,027, filed Jun. 16, 1999. Each ofthese prior applications is incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] The U.S. Government has certain rights in this invention pursuantto Contract No. DAAK60-97-K-9503 administered by the Defense AdvancedResearch Projects Agency.

BACKGROUND

[0003] The invention relates to sensors and sensor systems for detectinganalytes in fluids.

[0004] There is considerable interest in developing sensors that act asanalogs of the mammalian olfactory system (Lundstrom et al. (1991)Nature 352:47-50; Shurmer and Gardner (1992) Sens. Act. B 8:1-11;Shurmer and Gardner (1993) Sens. Act. B 15:32). In practice, mostchemical sensors suffer from some interference by responding to chemicalspecies that are structurally or chemically similar to the desiredanalyte. This interference is an inevitable consequence of the “lock”being able to fit a number of imperfect “keys”. Such interferences limitthe utility of such sensors to very specific situations.

[0005] Arrays of broadly cross-reactive sensors have been exploited toproduce response patterns that can be used to fingerprint, classify, andin some cases quantify analytes in fluids. Such arrays have beenproduced incorporating sensors including heated metal oxide thin filmresistors (Gardner et al. (1991) Sens. Act. B4:117-121; Gardner et al.(1992) Sens. Act. B 6:71-75), polymer sorption layers on the surfaces ofacoustic wave resonators(Grate and Abraham (1991) Sens. Act. B 3:85-111;Grate et al. (1993) Anal. Chem. 65:1868-1881), arrays of electrochemicalsensors (Stetter et al. (1986) Anal. Chem. 58:860-866; Stetter et al.(1990) Sens. Act. B 1:43-47; Stetter et al. (1993) Anal. Chem. Acta284:1-11), conductive polymers or composites that consist of regions ofconductors and regions of insulating organic materials (Pearce et al.(1993) Analyst 118:371-377; Shurmer et al. (1991) Sens. Act. B 4:29-33;Doleman et al. (1998) Anal. Chem. 70:2560-2654; Lonergan et al. Chem.Mater. 1996, 8:2298). Arrays of metal oxide thin film resistors,typically based on tin oxide (SnO₂) films that have been coated withvarious catalysts, yield distinct, diagnostic responses for severalvapors (Corcoran et al. (1993) Sens. Act. B 15:32-37). Surface acousticwave resonators are extremely sensitive to both mass and acousticimpedance changes of the coatings in array elements. Attempts have alsobeen made to construct arrays of sensors with conducting organic polymerelements that have been grown electrochemically through use of nominallyidentical polymer films and coatings. Moreover, Pearce et al., (1993)Analyst 118:371-377, and Gardner et al., (1994) Sensors and Actuators B18-19:240-243 describe polypyrrole based sensor arrays for monitoringbeer flavor. Shurmer (1990) U.S. Pat. No. 4,907,441, describes generalsensor arrays with particular electrical circuitry. U.S. Pat. No.4,674,320 describes a single chemoresistive sensor having asemiconductive material selected from the group consisting ofphthalocyanine, halogenated phthalocyanine and sulfonatedphthalocyanine, which was used to detect a gas contaminant. Other gassensors have been described by Dogan et al., Synth. Met. 60, 27-30(1993) and Kukla, et al. Films. Sens. Act. B., Chemical 37, 135-140(1996).

[0006] Sensor arrays formed from a plurality of composites that consistof regions of a conductor and regions of an insulating organic material,usually an organic polymer as described in U.S. Pat. No. 5,571,401, havesensitivities that are primarily dictated by the swelling-inducedsorption of a vapor into the composite material, and analytes that sorbto similar extents produce similar swellings and therefore producesimilar detected signals (Doleman, et al., (1998) Proc. Natl. Acad. Sci.U.S.A, 95, 5442-5447).

[0007] In these systems, the different responses from an analyteexposure to the array of sensors is used to identify the analyte. Otherproperties of the devices are designed to insure that otherwise allsensors are nominally equivalent so that the fluid containing theanalyte is delivered to all sensors equally effectively—for example, atthe same temperature—so that only the differences in sensors' responseproperties are being measured.

[0008] Although these sensor systems have some usefulness, there remainsa need in the art for highly-selective sensor arrays for detectinganalytes and resolving the components of complex mixtures.

SUMMARY OF THE INVENTION

[0009] The present artificial olfactory systems (or electronic noses)use arrays of many receptors to recognize an odorant. In such aconfiguration, the burden of recognition is not on highly specificreceptors, as in the traditional “lock-and-key” molecular recognitionapproach to chemical sensing, but lies instead on the distributedpattern processing of the olfactory bulb and the brain. The system takesadvantage of the spatio-temporal response differences between nominallyidentical sensors that are located at different positions in a fluidflow pattern.

[0010] In general, in one aspect, the invention provides a method ofdetecting an analyte in a fluid. The method includes providing a sensorarray including at least a first sensor and a second sensor in anarrangement having a defined fluid flow path; exposing the sensor arrayto a fluid including an analyte by introducing the fluid along the fluidflow path; measuring a response for the first sensor and the secondsensor; and detecting the presence of the analyte in the fluid based ona spatio-temporal difference between the responses for the first andsecond sensors.

[0011] Particular implementations of the invention can include one ormore of the following features. Detecting the presence of the analytecan include generating a spatio-temporal response profile indicative ofthe presence of the analyte based on the spatio-temporal differencebetween the responses for the first and second sensors. Thespatio-temporal response profile can be derived from time informationindicating the dependence of sensor response on time. The first sensorcan be exposed to the fluid before the second sensor, such that theresponse of the second sensor is delayed with respect to the response ofthe first sensor. The first sensor can be exposed to the fluid beforethe second sensor, such that the response of the second sensor ischanged in amplitude with respect to the response of the first sensor.The first sensor can include a sensing material; and the response of thefirst sensor can be greater than the response of the second sensor foran analyte having a high affinity for the sensing material. The firstand second sensors can be selected and arranged to provide a first delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a firstanalyte and a second delay between the response of the first sensor andthe response of the second sensor upon exposure of the sensor array to afluid including a second analyte. Measuring the response can includemeasuring the delay between the response of the first sensor and theresponse of the second sensor, and the spatio-temporal differencebetween the responses for the first and second sensors can be derivedfrom the delay. The method can include characterizing the analyte basedon the spatio-temporal difference between the responses. Exposing thesensor array to the fluid can include introducing the fluid at a varyingflow rate. Generating the spatio-temporal response profile can includegenerating flow information indicating the dependence of sensor responseon flow rate. The sensor array can include a plurality of cross-reactivesensors. The sensor array can include a plurality of sensors selectedfrom the group including surface acoustic wave sensors, quartz crystalresonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors. The firstand second sensors can include composites having regions of a conductingmaterial and regions of an insulating organic material. The first andsecond sensors can include composites having regions of a conductingmaterial and regions of a conducting organic material. The method caninclude generating a digital representation of the analyte based atleast in part on the responses of the first and second sensors. Themethod can include communicating the digital representation of theanalyte to a remote location for analysis.

[0012] In general, in another aspect, the invention provides a systemfor detecting an analyte in a fluid. The system includes a sensor arrayincluding at least a first sensor and a second sensor in an arrangementhaving a defined fluid flow path; a measuring apparatus coupled to thesensor array, the measuring apparatus being configured to detect aresponse from the first sensor and the second sensor upon exposure ofthe sensor array to a fluid; and a computer configured to generate dataindicating the presence of the analyte in the fluid based on aspatio-temporal difference between the responses for the first andsecond sensors.

[0013] Particular implementations of the invention can include one ormore of the following features. The data indicating the presence of theanalyte in the fluid can include a spatio-temporal response profilederived from the spatio-temporal difference between the responses forthe first and second sensors. The spatio-temporal response profile isderived from time information indicating the dependence of sensorresponse on time. The first sensor can occupy a first position in thearrangement and the second sensor a second position in the arrangement,such that the response of the second sensor is delayed in time withrespect to the response of the first sensor upon exposure of the sensorarray to the fluid. The first sensor can occupy a first position in thearrangement and the second sensor a second position in the arrangement,such that the response of the second sensor is changed in amplitude withrespect to the response of the first sensor upon exposure of the sensorarray to the fluid. The first sensor can include a sensing material, andthe response of the first sensor can be greater than the response of thesecond sensor for an analyte having a high affinity for the sensingmaterial. The first and second sensors can be selected and arranged toprovide a first delay between the response of the first sensor and theresponse of the second sensor upon exposure of the sensor array to afluid including a first analyte and a second delay between the responseof the first sensor and the response of the second sensor upon exposureof the sensor array to a fluid including a second analyte. The measuringapparatus can be configured to measure the delay between the response ofthe first sensor and the response of the second sensor; and thespatio-temporal difference between the responses for the first andsecond sensors can be derived from the delay. The computer can beconfigured to characterize the analyte based on the spatio-temporaldifference between the responses. The system can include a flowcontroller to introduce the fluid to the sensor array at a varying flowrate. The computer can be configured to generate flow informationindicating the dependence of sensor response on flow rate. The sensorarray can include a plurality of cross-reactive sensors. The sensorarray can include a plurality of sensors selected from the groupincluding surface acoustic wave sensors, quartz crystal resonators,metal oxide sensors, dye-coated fiber optic sensors, dye-impregnatedbead arrays, micromachined cantilever arrays, composites having regionsof conducting material and regions of insulating organic material,composites having regions of conducting material and regions ofconducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors. The firstand second sensors can include composites having regions of a conductingmaterial and regions of an insulating organic material. The first andsecond sensors can include composites having regions of a conductingmaterial and regions of a conducting organic material. The computer canbe configured to generate a digital representation of the analyte basedat least in part on the responses of the first and second sensors. Thesystem can include a communications port coupled to the computer forcommunicating the digital representation of the analyte to a remotelocation for analysis.

[0014] In general, in still another aspect, the invention provides asystem for detecting an analyte in a fluid. The system includes a sensorarray including a first sensor and a second sensor, a fluid inletproximate to the sensor array, and a measuring apparatus connected tothe sensor array. The fluid inlet defines a fluid flow pattern for theintroduction of a fluid onto the sensor array, such that the first andsecond sensors are located at different locations in the sensor arrayrelative to the fluid flow pattern. The measuring apparatus isconfigured to detect a response from the first sensor and the secondsensor upon exposure of the sensor array to a fluid. The responsesdefine a spatio-temporal difference between the responses for the firstand second sensors based on the locations of the sensors relative to thefluid flow pattern.

[0015] Particular implementations of the invention can include one ormore of the following features. The spatio-temporal difference can bederived from time information indicating the dependence of sensorresponse on time. The first sensor can occupy a first position relativeto the fluid flow pattern and the second sensor a second positionrelative to the fluid flow pattern, such that the response of the secondsensor is delayed with respect to the response of the first sensor uponexposure of the sensor array to the fluid. The first sensor can occupy afirst position relative to the fluid flow pattern and the second sensora second position relative to the fluid flow pattern, such that theresponse of the second sensor is changed in amplitude with respect tothe response of the first sensor upon exposure of the sensor array tothe fluid. The first sensor can include a sensing material and theresponse of the first sensor can be greater than the response of thesecond sensor for an analyte having a high affinity for the sensingmaterial. The first and second sensors can be selected and arranged toprovide a first delay between the response of the first sensor and theresponse of the second sensor upon exposure of the sensor array to afluid including a first analyte and a second delay between the responseof the first sensor and the response of the second sensor upon exposureof the sensor array to a fluid including a second analyte. The measuringapparatus can be configured to measure the delay between the response ofthe first sensor and the response of the second sensor, and thespatio-temporal difference between the responses for the first andsecond sensors can be derived from the delay. The system can include acomputer configured to characterize the analyte based on thespatio-temporal difference between the responses. The system can includea flow controller to introduce the fluid to the sensor array at avarying flow rate. The measuring apparatus can be configured to measureflow information indicating the dependence of sensor response on flowrate. The sensor array can include a plurality of cross-reactivesensors. The system sensor array can include a plurality of sensorsselected from the group including surface acoustic wave sensors, quartzcrystal resonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors. The firstand second sensors can include composites having regions of a conductingmaterial and regions of an insulating organic material. The first andsecond sensors can include composites having regions of a conductingmaterial and regions of a conducting organic material. The computer canbe configured to generate a digital representation of the analyte basedat least in part on the responses of the first and second sensors.

[0016] In general, in still another aspect, the invention provides asystem for detecting an analyte in a fluid. The system includes a sensorarray including a first sensor and a second sensor; a fluid flowexposing the first and second sensors to a fluid, such that the firstand second sensors occupy different locations in the sensor arrayrelative to the fluid flow; and a measuring apparatus connected to thesensor array. The measuring apparatus is configured to detect a responsefrom the first and second sensors upon exposure of the sensor array tothe fluid flow. The responses define a spatio-temporal difference basedon the locations of the sensors in the sensor array relative to thefluid flow.

[0017] Particular implementations of the invention can include one ormore of the following features. The spatio-temporal difference can bederived from time information indicating the dependence of sensorresponse on time. The first sensor can occupy a first position relativeto the fluid flow and the second sensor a second position relative tothe fluid flow, such that the response of the second sensor is delayedwith respect to the response of the first sensor upon exposure of thesensor array to the fluid. The first sensor can occupy a first positionrelative to the fluid flow and the second sensor occupies a secondposition relative to the fluid flow, such that the response of thesecond sensor is changed in amplitude with respect to the response ofthe first sensor upon exposure of the sensor array to the fluid. Thefirst sensor can include a sensing material, and the response of thefirst sensor can be greater than the response of the second sensor foran analyte having a high affinity for the sensing material. The firstand second sensors can be selected and arranged to provide a first delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a firstanalyte and a second delay between the response of the first sensor andthe response of the second sensor upon exposure of the sensor array to afluid including a second analyte. The measuring apparatus can beconfigured to measure the delay between the response of the first sensorand the response of the second sensor, and the spatio-temporaldifference between the responses for the first and second sensors can bederived from the delay. The system can include a computer configured tocharacterize the analyte based on the spatio-temporal difference betweenthe responses. The system can include a flow controller to vary the rateof the fluid flow. The measuring apparatus can be configured to measureflow information indicating the dependence of sensor response on flowrate. The sensor array can include a plurality of cross-reactivesensors. The sensor array can include a plurality of sensors selectedfrom the group including surface acoustic wave sensors, quartz crystalresonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors. The firstand second sensors can include composites having regions of a conductingmaterial and regions of an insulating organic material. The first andsecond sensors can include composites having regions of a conductingmaterial and regions of a conducting organic material. The computer canbe configured to generate a digital representation of the analyte basedat least in part on the responses of the first and second sensors.

[0018] In general, in still another aspect, the invention provides asensor array for detecting an analyte in a fluid. The sensor arrayincludes a substrate; a first sensor coupled to the substrate at a firstlocation; and a second sensor coupled to the substrate at a secondlocation, such that the first and second sensors occupy differentlocations in the sensor array relative to a fluid flow path.

[0019] Particular implementations of the invention can include one ormore of the following features. The first sensor can occupy a firstposition relative to the fluid flow path and the second sensor a secondposition relative to the fluid flow path, the first sensor beingconfigured to provide a first response upon exposure of the sensor arrayto a fluid and the second sensor being configured to provide a secondresponse upon exposure of the sensor array to the fluid, such that thesecond response is delayed with respect to the first response uponexposure of the sensor array to the fluid. The first sensor can providea first time-dependent response upon exposure of the sensor array to afluid, and the second sensor can provide a second time-dependentresponse upon exposure of the sensor array to the fluid. The firstsensor can occupy a first position relative to the fluid flow path andthe second sensor a second position relative to the fluid flow path,such that the second time-dependent response is changed in amplitudewith respect to the first time-dependent response upon exposure of thesensor array to the fluid. The first sensor can include a sensingmaterial, and the response of the first sensor can be greater than theresponse of the second sensor for an analyte having a high affinity forthe sensing material. The first and second sensors can be selected andarranged to provide a first delay between a response of the first sensorand a response of the second sensor upon exposure of the sensor array toa fluid including a first analyte and a second delay between a responseof the first sensor and a response of the second sensor upon exposure ofthe sensor array to a fluid including a second analyte. The sensor arraycan include a plurality of cross-reactive sensors. The sensor array caninclude a plurality of sensors selected from the group including surfaceacoustic wave sensors, quartz crystal resonators, metal oxide sensors,dye-coated fiber optic sensors, dye-impregnated bead arrays,micromachined cantilever arrays, composites having regions of conductingmaterial and regions of insulating organic material, composites havingregions of conducting material and regions of conducting orsemiconducting organic material, chemically-sensitive resistor orcapacitor films, metal-oxide-semiconductor field effect transistors, andbulk organic conducting polymeric sensors. The first and second sensorscan include composites having regions of a conducting material andregions of an insulating organic material. The first and second sensorscan include composites having regions of a conducting material andregions of a conducting organic material.

[0020] Advantages that can be seen in implementations of the inventioninclude one or more of the following. Taking advantage of aspatio-temporal property of a sensor array can impart very usefulinformation on analyte identification and detection relative to arrayswhere no spatiotemporal information is available because all sensors arenominally in identical positions with respect to the fluid flowcharacteristics and are exposed to the analyte at nominally identicaltimes during the fluid sampling experiment. Electronics can beimplemented to record the time delay between sensor responses and to usethis information to characterize the analyte of interest in the fluid.This mode can also be advantageous because it can allow automaticnulling of any sensor drift, environmental variations (such astemperature, humidity, etc.) and the like. Also, a complex odor mixturecan be better resolved into its components based on the spatiotemporalcharacteristics of the array response relative only to the differencesin fingerprints on the various sensors types in the array. Additionally,these techniques can be used in conjunction with differential types ofmeasurements to selectively detect only certain classes or types ofanalytes, because the detection can be gated to only focus on signalsthat exhibit a desired correlation time between their responses on thesensors that are in different exposure times relative to the sensorresponse on the first sensor that detects an analyte.

BRIEF DESCRIPTION OF THE FIGURES

[0021] These and other objects of the present invention will now bedescribed in detail with reference to the accompanying drawings, inwhich:

[0022]FIG. 1 is a block diagram illustrating a system for detecting ananalyte in a fluid.

[0023]FIG. 2 is a flow diagram illustrating a method of detecting ananalyte in a fluid.

[0024]FIG. 3 illustrates one implementation of a system for detecting ananalyte in a fluid according to the invention.

[0025]FIGS. 4a-b are plots of sensor response as a function of time forthe sensor array shown in FIG. 3.

[0026]FIGS. 5a-b are plots of response as a function of flow rate andlinear flow rate, respectively, for one sensor in the array shown inFIG. 3.

[0027]FIG. 6 is a schematic diagram illustrating an alternateimplementation of a system for detecting an analyte in a fluid accordingto the invention.

[0028]FIG. 7 is a graph illustrating sensor response as a function ofsensor position in an experiment involving the array shown in FIG. 6.

[0029]FIG. 8 is a graph illustrating a resistance versus time profilecalculated for a sensor array comprising eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black composite sensors.

[0030]FIG. 9 is a graph illustrating a plot of sensor output versus timefor the sensor array of FIG. 8.

[0031]FIGS. 10a-b are graphs illustrating the resistance (delta ppm)behavior and sensor output as a function of time for a single exposurehaving the largest sensor output for the experiment of FIGS. 8 and 9.

[0032]FIGS. 11a-b are graphs illustrating the resistance (delta ppm)behavior and sensor output as a function of time for a single exposurehaving an intermediate sensor output for the experiment of FIGS. 8 and9.

[0033]FIGS. 12a-b are graphs illustrating the resistance (delta ppm)behavior and sensor output as a function of time for a single exposurehaving the smallest sensor output for the experiment of FIGS. 8 and 9.

[0034]FIGS. 13a-b are graphs illustrating the resistance (delta ppm)behavior and sensor output as a function of time for two “near miss”background windows for the experiment of FIGS. 8 and 9.

[0035]FIGS. 14a-b are graphs illustrating resistance transients andchange in resistance as a function of time showing the dependence ofsignal from a ventilated sensor array on flow rate.

[0036]FIGS. 15a-c are graphs illustrating response transients at varyingflow rates; response slope as a function of flow rate through thesensor; and signal to noise after 5 s exposure as a function of flowrate, respectively, for an experiment involving the ventilated sensorarray of FIGS. 14a-b.

DETAILED DESCRIPTION OF THE INVENTION

[0037]FIG. 1 illustrates a system 100 for detecting an analyte in afluid. System 100 includes a sensor array 110, in which an arrangementof a plurality of sensors 120 defines a fluid channel 130. Optionally,sensor array 110 is configured to include one or more fluid channels 140in addition to fluid channel 130, each fluid channel 140 including anadditional plurality of sensors 150. A fluid to be analyzed, which maybe in gaseous or liquid form, is exposed to sensor array 110 throughfluid inlet 160, for example from fluid reservoir 170. Response signalsfrom the sensors 120, 150 in sensor array 110 resulting from exposure ofthe fluid to the sensor array are received and processed in detector180, which may include, for example, signal-processing electronics, ageneral-purpose programmable digital computer system of conventionalconstruction, or the like.

[0038] A method 200 of using system 100 to detect the presence of ananalyte in a fluid is illustrated in FIG. 2. A fluid including ananalyte is introduced onto a sensor array 110 (step 210). According to aflow pattern defined by the configuration of array 110 or by theintroduction of the fluid, at a time t the fluid interacts with a firstsensor or sensors (step 220). Detector 180 detects and records responsesignals from the first sensor(s) (step 230). The fluid then interactswith a second sensor or sensors at a time t+δ (step 240), and detector180 detects and records response signals from the second sensor(s) (step250). Steps 230 and 240 are repeated as the fluid travels across array110, until each sensor in the array has been exposed to the fluid andthe corresponding response signal recorded by detector 180 (The NObranch of step 260). The recorded response signals are then processed todetect and or characterize an analyte or combination of analytes in thefluid (step 270).

[0039] Sensors 120, 180 can include any of a variety of known sensors,including, for example, surface acoustic wave sensors, quartz crystalresonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, bulk organic conducting polymeric sensors, and other knownsensor types. Techniques for constructing arrays of such sensors areknown, as disclosed in Harsanyi, G., Polymer Films in SensorApplications (Technomic Publishing Co., Basel, Switzerland, 1995), andU.S. Pat. Nos. 6,017,440, 6,013,229 and 5,911,872 and co-pending U.S.patent application Ser. No. 09/409,644, filed Oct. 1, 1999, which areincorporated by reference herein. Techniques for fabricating particularsensor types are disclosed in Ballantine, D. S.; Rose, S. L.; Grate, J.W.; Wohltjen, H. Anal. Chem. 1986, 58, 3058; Grate, J. W.; Abraham, M.H. Sens. Actuators B 1991, 3, 85; Grate, J. W.; Rosepehrsson, S. L.;Venezky, D. L.; Klusty, M.; Wohltjen, H. Anal. Chem. 1993, 65, 1868;Nakamoto, T.; Fukuda, A.; Moriizumi, T. Sens. Actuators B 1993, 10, 85(surface acoustic wave (SAW) devices), Gardner, J. W.; Shurmer, H. V.;Corcoran, P. Sens. Actuators B 1991, 4, 117; Gardner, J. W.; Shurmer, H.V.; Tan, T. T. Sens. Actuators B 1992, 6, 71; Corcoran, P.; Shurmer, H.V.; Gardner, J. W. Sens. Actuators B 1993, 15, 32 (tin oxide sensors),Shurmer, H. V.; Corcoran, P.; Gardner, J. W. Sens. Actuators B 1991, 4,29; Pearce, T. C.; Gardner, J. W.; Friel, S.; Bartlett, P. N.; Blair, N.Analyst 1993, 118, 371 (conducting organic polymers), Freund, M. S.;Lewis, N. S. Proc. Natl. Acad. Sci 1995, 92, 2652 (materials havingregions of conductors and regions of insulating organic material),White, J.; Kauer, J. S.; Dickinson, T. A.; Walt, D. R. Anal. Chem. 1996,68, 2191 (dye-impregnated polymer films on fiber optic sensors), Butler,M. A.; Ricco, A. J.; Buss, R. J. Electrochem. Soc. 1990, 137, 1325;Hughes, R. C.; Ricco, A. J.; Butler, M. A.; Pfeifer, K. B. J. Biochem.and Biotechnol. 1993, 41, 77 (polymer-coated micromirrors), Slater, J.M.; Paynter, J. Analyst 1994, 119, 191; Slater, J. M.; Watt, E. J.Analyst 1991, 116, 1125 (quartz crystal microbalances (QCMs)), Keyvani,D.; Maclay, J.; Lee, S.; Stetter, J.; Cao, Z. Sens. Actuators B 1991, 5,199 (electrochemical gas sensors), Zubkans, J.; Spetz, A. L.; Sundgren,H.; Winquist, F.; Kleperis, J.; Lusis, A.; Lundstrom, I. Thin SolidFilms 1995, 268, 140 (chemically sensitive field-effect transistors) andLonergan, M. C.; Severin, E. J.; Doleman, B. J.; Beaber, S. A.; Grubbs,R. H.; Lewis, N. S. Chem. Mater. 1996, 8, 2298 carbon black-polymercomposite chemiresistors ). Additional sensor array fabricationtechniques are disclosed in Albert, K. J., Lewis, N. S., et al.,Cross-Reactive Chemical Sensor Arrays, Chemical Reviews, 2000, 100 (inpress) and the references cited therein.

[0040] In one implementation, sensor array 110 incorporates multiplesensing modalities, for example comprising a spatial arrangement ofcross-reactive sensors 120, 180 selected from known sensor types, suchas those listed above, such that a given analyte elicits a response frommultiple sensors in the array and each sensor responds to many analytes.Preferably, the sensors in the array 110 are broadly cross-reactive,meaning each sensor in the array responds to multiple analytes, and, inturn, each analyte elicits a response from multiple sensors.

[0041] Sensor arrays allow expanded utility because the signal for animperfect “key” in one channel can be recognized through informationgathered on another, chemically or physically dissimilar channel in thearray. A distinct pattern of responses produced over the collection ofsensors in the array can provide a fingerprint that allowsclassification and identification of the analyte, whereas suchinformation would not have been obtainable by relying on the signalsarising solely from a single sensor or sensing material. By developingan empirical catalogue of information on chemically diversesensors—made, for example, with varying ratios of semiconductive,conducting, and insulating components and by differing fabricationroutes—sensors can be chosen that are appropriate for the analytesexpected in a particular application, their concentrations, and thedesired response times. Further optimization can then be performed in aniterative fashion as feedback on the performance of an array underparticular conditions becomes available.

[0042] The sensor arrays of system 100 provide still further benefits byincorporating spatio-temporal response information that is exploited bydetector 180 to aid in analyte detection and identification. Takingadvantage of a spatio-temporal property of a sensor array can impartuseful information on analyte detection and identification relative toarrays where no spatiotemporal information is available because allsensors are nominally in identical positions with respect to the fluidflow characteristics and are exposed to the analyte at nominallyidentical times during the fluid sampling experiment. Electronics can beimplemented in detector 180 to record a time delay between sensorresponses and to use this information to characterize the analyte ofinterest in the fluid. This mode can also be advantageous because it canallow automatic nulling of any sensor drift, environmental variations(such as temperature, humidity, etc.) and the like. Also, a complexanalyte mixture can be better resolved into its components based on thespatiotemporal characteristics of the array response relative only tothe differences in fingerprints on the various sensors types in thearray. Additionally, the method can be used in conjunction withdifferential types of measurements to selectively detect only certainclasses or types of analytes, because the detection can be gated to onlyfocus on signals that exhibit a desired correlation time between theirresponses on the sensors that are in different exposure times relativeto the sensor response on the first sensor that detects an analyte.

[0043] Thus, for example, sensor arrays 110 can be configured such thatlow vapor pressure analytes in the gas phase will have a high affinitytowards the sensors and will sorb strongly to them. This strong sorptionproduces a strong response at the first downstream sensor that theanalyte encounters, a weaker response at the second downstream sensor,and a still weaker response at other downstream sensors. Differentanalytes will produce a detectable and useful time delay between theresponse of the first sensor and the response of the other downstreamsensors. As a result, detector 180 can use the differences in responsetime and amplitude to detect and characterize analytes in a carrierfluid, analogous to the use of gas chromatography retention times, whichare well known in the gas chromatography literature and art.

[0044] Spatio-temporal information can be obtained from an array of twoor more sensors by varying the sensors' exposure to the fluid containingthe analyte across the array (e.g., by generating a spatial and/ortemporal gradient across the array), thereby allowing responses to bemeasured simultaneously at various different exposure levels and forvarious different sensor compositions. For example, an array 110 ofsensors 120, 150, can be configured to vary the composition of thesensors in the horizontal direction across the array, such that sensorcomposition in the vertical direction across the array remains constant.One may then create a spatio-temporal gradient in the vertical directionacross the array—for example, by introducing the fluid from the top ofthe array and providing for fluid flow vertically down the array,thereby allowing the simultaneous analysis of chemical analytes atdifferent sensor compositions and different exposure levels. Similarly,in an array 110 including a plurality of different sensors 120, 150(i.e., an array in which each sensor is of a different type orcomposition), spatio-temporal variation can be introduced bysystematically varying the flow rate at which the analyte-containingfluid is exposed to the sensors in the array. Again, in thisimplementation, measuring the response of each of the sensors 120, 150at a variety of different flow rates allows the simultaneous analysis ofanalytes at different sensor compositions and different exposure levels.

[0045] Thus, in one implementation, the sensors 120, 150 defining eachfluid channel 130, 140 are nominally identical—that is, the sensors 120,150 within a given fluid channel 130, 140 are identical. In contrast,sensor array 110 incorporates a predetermined inter-sensor variation inthe chemistry, structure or composition of the sensors 120, 150 betweenfluid channels 130, 140. The variation may be quantitative and/orqualitative. For example, different channels 130, 140 can be constructedto incorporate sensors of different types, such as incorporating aplurality of nominally identical metal oxide gas sensors in a fluidchannel 130, a plurality of conducting polymer sensors in an adjacentfluid channel 140, and so on across array 110. Alternatively,compositional variation can be introduced by varying the concentrationof a conductive or semiconductive organic material in a composite sensoracross fluid channels. In still another variation, a variety ofdifferent organic materials may be used in sensors in differentchannels. Similar patterns of introducing compositional variation intosensor arrays 110 will be readily apparent to those skilled in the art.

[0046] Although FIG. 1 illustrates fluid channels 130, 140 as linearchannels extending in just one direction, sensor arrays can beconfigured to provide similar fluid channels having differentgeometries—for example, arrays with sensors arranged in two or moredirections relative to the fluid flow, such as a circular array having aradial arrangement of sensors around a fluid introduction point. Andalthough sensor array 110 has been described as incorporating one ormore fluid channels each comprising a plurality of nominally identicalsensors, those skilled in the art will recognize that the techniquesdescribed herein can be used to generate useful spatio-temporalinformation from arrays including a plurality of sensors all ofdifferent chemistry, structure or composition, with the fluid path beingdefined by the introduction of the fluid onto the array. In thisimplementation, spatio-temporal response data can be generated byintroducing the fluid onto the array at varying flow rates, for example,by using a flow controller of known construction to systematically varythe rate at which the fluid is introduced over time. Alternatively, flowrate variation can be introduced by simply exposing the array to anaturally varying fluid flow, such as a flow of air.

[0047] A system 100 is fabricated by electrically coupling the sensorleads of an array of differently responding sensors to an electricalmeasuring device 180. The device measures changes in signal at eachsensor of the array, preferably simultaneously and preferably over time.The signal is an electrical resistance, impedance or other physicalproperty of the material in response to the presence of the analyte inthe fluid. Frequently, the device 180 includes signal processing meansand is used in conjunction with a computer and data structure forcomparing a given response profile to a structure-response profiledatabase for qualitative and quantitative analysis. Typically an array110 for use in system 100 comprises usually at least ten, often at least100, and perhaps at least 1000 different sensors though with massdeposition fabrication techniques described herein or otherwise known inthe art, arrays of on the order of at least one million sensors arereadily produced.

[0048] In one mode of operation with an array of sensors, each sensorprovides a first electrical signal when the sensor is contacted with afirst fluid comprising a first chemical analyte, and a second electricalsignal between its conductive leads when the sensor is contacted with asecond fluid comprising a second, different chemical analyte. The fluidsmay be liquid or gaseous in nature. The first and second fluids mayreflect samples from two different environments, a change in theconcentration of an analyte in a fluid sampled at two time points, asample and a negative control, etc. The sensor array necessarilycomprises sensors that respond differently to a change in an analyteconcentration or identity, i.e., the difference between the first andsecond electrical signal of one sensor is different from the differencebetween the first and second electrical signals of another sensor.

[0049] In one embodiment, the temporal response of each sensor (forexample, signal as a function of time) is recorded. The temporalresponse of each sensor can be normalized to a maximum percent increaseand percent decrease in signal that produces a response patternassociated with the exposure of the analyte. By iterative profiling ofknown analytes, a structure-function database correlating analytes andresponse profiles is generated. Unknown analytes can then becharacterized or identified using response pattern comparison andrecognition algorithms. Accordingly, analyte detection systemscomprising sensor arrays, an electrical measuring device for detectingsignal at each sensor, a computer, a data structure of sensor arrayresponse profiles, and a comparison algorithm are provided. In anotherembodiment, the electrical measuring device is an integrated circuitcomprising neural network-based hardware and a digital-analog converter(DAC) multiplexed to each sensor, or a plurality of DACs, each connectedto different sensor(s).

[0050] The desired signals if monitored as dc electrical resistances forthe various sensor elements in an array can be read merely by imposing aconstant current source through the resistors and then monitoring thevoltage across each resistor through use of a commercial multiplexable20 bit analog-to-digital converter. Such signals are readily stored in acomputer that contains a resident algorithm for data analysis andarchiving. Signals can also be preprocessed either in digital or analogform; the latter might adopt a resistive grid configuration, forexample, to achieve local gain control. In addition, long timeadaptation electronics can be added or the data can be processeddigitally after it is collected from the sensors themselves. Thisprocessing could be on the same chip as the sensors but also couldreside on a physically separate chip or computer.

[0051] Data analysis can be performed using standard chemometric methodssuch as principal component analysis and SIMCA, which are available incommercial software packages that run on a PC or which are easilytransferred into a computer running a resident algorithm or onto asignal analysis chip either integrated onto, or working in conjunctionwith, the sensor measurement electronics. The Fisher linear discriminantis one preferred algorithm for analysis of the data, as described below.In addition, more sophisticated algorithms and supervised orunsupervised neural network based learning/training methods can beapplied as well (Duda, R. O.; Hart, P. E. Pattern Classification andScene Analysis; John Wiley & Sons: New York, 1973, pp 482).

[0052] The signals can also be useful in forming a digitallytransmittable representation of an analyte in a fluid. Such signalscould be transmitted over the Internet in encrypted or in publiclyavailable form and analyzed by a central processing unit at a remotesite, and/or archived for compilation of a data set that could be minedto determine, for example, changes with respect to historical mean“normal” values of the breathing air in confined spaces, of human breathprofiles, and of a variety of other long term monitoring situationswhere detection of analytes in fluids is an important value-addedcomponent of the data.

[0053] An array of 20-30 different sensors is sufficient for manyanalyte classification tasks but larger array sizes can be implementedas well. Temperature and humidity can be controlled but because apreferred mode is to record changes relative to the ambient baselinecondition, and because the patterns for a particular type andconcentration of odorant are generally independent of such baselineconditions, it is not critical to actively control these variables insome implementations of the technology. Such control could be achievedeither in open-loop or closed-loop configurations.

[0054] The sensor arrays disclosed herein could be used with or withoutpreconcentration of the analyte depending on the power levels and othersystem constraints demanded by the user. Regardless of the samplingmode, the characteristic patterns (both from amplitude and temporalfeatures, depending on the most robust classification algorithm for thepurpose) associated with certain disease states and other volatileanalyte signatures can be identified using the sensors disclosed herein.These patterns are then stored in a library, and matched against thesignatures emanating from the sample to determine the likelihood of aparticular odor falling into the category of concern (disease ornondisease, toxic or nontoxic chemical, good or bad polymer samples,fresh or old fish, fresh or contaminated air etc.).

[0055] Analyte sampling will occur differently in the variousapplication scenarios. For some applications, direct headspace samplescan be collected using either single breath and urine samples in thecase of sampling a patient's breath for the purpose of disease or healthstate differentiation and classification. In addition, extended breathsamples, passed over a Tenax, Carbopack, Poropak, Carbosieve, or othersorbent preconcentrator material, can be obtained when needed to obtainrobust intensity signals. The absorbent material of the fluidconcentrator can be, but is not limited to, a nanoporous material, amicroporous material, a chemically reactive material, a nonporousmaterial and combinations thereof. In certain instances, the absorbentmaterial can concentrate the analyte by a factor that exceeds a factorof about 10⁵, or by a factor of about 10² to about 10⁴. In anotherembodiment, removal of background water vapor is conducted inconjunction, such as concomitantly, with the concentration of theanalyte. Once the analyte is concentrated, it can be desorbed using avariety of techniques, such as heating, purging, stripping, pressuringor a combination thereof.

[0056] Breath samples can be collected through a straw or suitable tubein a patient's mouth that is connected to the sample chamber (orpreconcentrator chamber), with the analyte outlet available for captureto enable subsequent GC/MS or other selected laboratory analyticalstudies of the sample. In other applications, headspace samples ofodorous specimens can be analyzed and/or carrier gases can be used totransmit the analyte of concern to the sensors to produce the desiredresponse. In still other cases, the analyte will be in a liquid phaseand the liquid phase will be directly exposed to the sensors; in othercases the analyte will undergo some separation initially and in yetother cases only the headspace of the analyte will be exposed to thesensors.

[0057] Using the device of the present invention, the analyte can beconcentrated from an initial sample volume of about 10 liters and thendesorbed into a concentrated volume of about 10 milliliters or less,before being presented to the sensor array.

[0058] Suitable commercially available adsorbent materials include butare not limited to, Tenax TA, Tenax GR, Carbotrap, Carbopack B and C,Carbotrap C, Carboxen, Carbosieve SIII, Porapak, Spherocarb, andcombinations thereof. Preferred adsorbent combinations include, but arenot limited to, Tenax GR and Carbopack B; Carbopack B and CarbosieveSIII; and Carbopack C and Carbopack B and Carbosieve SIII or Carboxen1000. Those skilled in the art will know of other suitable absorbentmaterials.

[0059] In another embodiment, removal of background water vapor isconducted in conjunction, such as concomitantly, with the concentrationof the analyte. Once the analyte is concentrated, it can be desorbedusing a variety of techniques, such as heating, purging, stripping,pressuring or a combination thereof. In these embodiments, the sampleconcentrator is wrapped with a wire through which current can be appliedto heat and thus, desorb the concentrated analyte. The analyte isthereafter transferred to the sensor array.

[0060] In some cases, the array will not yield a distinct signature ofeach individual analyte in a region, unless one specific type of analytedominates the chemical composition of a sample. Instead, a pattern thatis a composite, with certain characteristic temporal features of thesensor responses that aid in formulating a unique relationship betweenthe detected analyte contents and the resulting array response, will beobtained.

[0061] In a preferred embodiment of signal processing, the Fisher lineardiscriminant searches for the projection vector, w, in the detectorspace that maximizes the pairwise resolution factor, i.e., rf, for eachset of analytes, and reports the value of rf along this optimal lineardiscriminant vector. The rf value is an inherent property of the dataset and does not depend on whether principal component space or originaldetector space is used to analyze the response data. This resolutionfactor is basically a multi-dimensional analogue to the separationfactors used to quantify the resolving power of a column in gaschromatography, and thus the rf value serves as a quantitativeindication of how distinct two patterns are from each other, consideringboth the signals and the distribution of responses upon exposure to theanalytes that comprise the solvent pair of concern. For example,assuming a Gaussian distribution relative to the mean value of the datapoints that are obtained from the responses of the array to any givenanalyte, the probabilities of correctly identifying an analyte as a or bfrom a single presentation when a and b are separated with resolutionfactors of 1.0, 2.0 or 3.0 are approximately 76%, 92% and 98%respectively.

[0062] To compute the rf, from standard vector analysis, the meanresponse vector, x_(a), of an n-sensor array to analyte a is given asthe n-dimensional vector containing the mean autoscaled response of eachsensors, A_(aj), to the a^(th) analyte as components such that

x_(a)=(A_(a1), A_(a2), . . . A_(an))

[0063] The average separation, |d|, between the two analytes, a and b,in the Euclidean sensor response space is then equal to the magnitude ofthe difference between x_(a) and x_(b). The noise of the sensorresponses is also important in quantifying the resolving power of thesensor array. Thus the standard deviations, s_(a,d) and s_(b,d),obtained from all the individual array responses to each of a and balong the vector d, are used to describe the average separation andultimately to define the pairwise resolution factor as

rf=d _(w)/{square root}(σ² _(a,w)+σ² _(b,w)).

[0064] Even if the dimensionality of odor space is fairly small, say onthe order of 10¹, there is still interest in being able to model thebiological olfactory system in its construction of arrays consisting oflarge numbers of receptor sites. Furthermore, even if a relatively smallnumber (<10) of ideal sensors could indeed span odor space, it is notlikely that such ideal sensors could be identified. In practice,correlations between the elements of a sensor array will necessitate amuch larger number of sensors to successfully distinguish molecules.Furthermore, performance issues such as response time, signal averaging,or calibration ranges may require multiple sensors based on eachmaterial. Analysis of regions will add additional degrees of freedom ifthe components of the region are to be individually identified and willrequire large numbers of sensors. Fabrication of large numbers ofsensors also enables the use of very powerful coherent signal detectionalgorithms to pull a known, but small amplitude, signal, out of a noisybackground. Because of all of these issues, the number of sensorsrequired to successfully span odor space in a practical device mayrapidly multiply from the minimum value defined by the dimensionality ofsmell space.

[0065] The sensor arrays disclosed herein act as “electronic noses” tooffer ease of use, speed, and identification of analytes and/or analyteregions all in a portable, relatively inexpensive implementation. A widevariety of analytes and fluids may be analyzed by the disclosed arraysso long as the subject analyte is capable generating a differentialresponse across a plurality of sensors of the array. Analyteapplications include broad ranges of chemical classes such as organicsincluding, for example, alkanes, alkenes, alkynes, dienes, alicyclichydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls,carbanions, biogenic amines, thiols, polynuclear aromatics andderivatives of such organics, e.g., halide derivatives, etc.,biomolecules such as sugars, isoprenes and isoprenoids, fatty acids andderivatives, etc.

[0066] Commercial applications of the arrays include environmentaltoxicology and remediation, materials quality control, food andagricultural products monitoring, fruit ripening control, fermentationprocess monitoring and control applications, flavor composition andidentification, cosmetic/perfume/fragrance formulation, anaestheticdetection, ambient air quality monitoring, emissions monitoring andcontrol, leak detection and identification, H₂S monitoring, automobileoil or radiator fluid monitoring, hazardous spill identification,fugitive emission identification, medical diagnostics, detection andclassification of bacteria and microorganisms both in vitro and in vivofor biomedical uses and medical diagnostic uses, infectious diseasedetection, body fluids analysis, drug discovery, telesurgery, breathalcohol analyzers, illegal substance detection and identification, arsoninvestigation, smoke and fire detection, combustible gas detection,explosives and chemical weapons detection and identification, enclosedspace surveying, personal identification, automatic ventilation controlapplications (cooking, smoking, etc.), air intake monitoring, and thelike.

[0067] The following examples are offered by way of illustration and notby way of limitation.

EXAMPLES

[0068] In the following examples, broadly responsive sensor arrays wereconstructed based on carbon black composites for various vapor detectiontasks. Individual sensor elements were constructed from films consistingof carbon black particles dispersed into insulating organic polymers.The carbon black endows electrical conductivity to the films, whereasthe different organic polymers are the source of chemical diversitybetween elements in the sensor array. Swelling of the polymer uponexposure to a vapor increases the resistance of the film, therebyproviding an extraordinarily simple means for monitoring the presence ofa vapor. Because different polymer compositions are present on eachsensor element, an array of elements responds to a wide variety ofvapors (or complex mixtures of vapors) in a distinctive, identifiablefashion. The electrical resistance signals that are output from thearray can be readily integrated into software- or hardware-baseddecision systems, allowing for an integration of sensing and analysisfunctions into a compact, low-power, simple vapor sensor.

[0069] Preparation of Sensor Arrays.

[0070] In general, arrays of nominally identical polymer-carbon blackcomposite sensors were constructed by spray-coating a ceramic substratehaving pairs of leads spaced 1.0 mm apart. Each sensor was sprayed froma suspension of carbon black in a solvent that dissolved the polymer,and the components had a weight percentage of 20% of carbon black todissolved polymer. The leads were 3.5 mm in length and 0.1 mm in widthand were interdigitated such that the total width contacting a givensensor film was 3.0 mm. The output of every pair of leads from eachsensor were connected to a printed circuit board equipped withelectronics that read the resistance signals to a precision of <5 ppmevery 0.5 s on the entire bank of sensors.

Example 1

[0071] Referring to FIG. 3, an array 300 of eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black composite sensors 301-308 wasconstructed as described above. A stream 310 of 2,4-dinitrotoluene (DNT)in air at 5% of its vapor pressure was directed onto the surface, suchthat the stream was directed at sensor 304 and then moved radially inboth directions across the array.

[0072] 5% of the vapor pressure of DNT at 20° C. was selected as adilution of DNT that would deliver less than 10 ppb of the compound tothe sensors. The DNT source was a tube approximately a meter in lengththat held about 180 g of loosely packed, granulated DNT. The air flowthrough the tube was 0.5 L-min⁻¹. This air flow was mixed with, andtherefore diluted by a flow of 9.5 L-min⁻¹ of air (from the same source)that did not flow through the DNT tube. At this dilution, the upperlimit of the DNT concentration is 7 ppb, because the vapor pressure ofDNT at room temperature is approximately 140 ppb. If saturation of thebackground air through the DNT tube occurred, and if no DNT stuck to thewalls of the tubing after mixing with the pure background analyte flow,this dilution would produce a concentration of 7 ppb of DNT. However,analyses performed by sorbing the analyte flow onto Tenax for a 10minute period (to obtain enough DNT with which to perform analysis) andthen analyzing the desorbed products with a GC-ECD system indicated thatthe actual DNT concentration exiting the tubing and available to bedetected was approximately 0.2-0.4 ppb.

[0073] Flows were controlled by mass flow controllers in a computercontrolled system that has been described in detail in Severin, E. J.,Doleman, B. J., Lewis, N. S., Anal. Chem., 2000, 72, 658. A union-T wasused to mix the background and analyte-containing gases, and a shortTeflon tube was connected to the output of the union to direct the gastoward the bank of sensors. The array substrate was placed such that thesensors were perpendicular to the output of the DNT flow and wereapproximately 0.5 cm from the end of the tubing.

[0074] The DNT flow was delivered at four flow rates: 0.5 liters/min,1.0 liters/min, 3.0 liters/min and 6.0 liters/min. Results reporting thesensor response as a function of time for the eight sensors are plottedin FIGS. 4a-b. Sensor 304, in the center of the array and directly underthe flow, responds faster and to a greater extent for each of the testedflow rates. The flow rate dependence of the response for this sensor isillustrated in FIGS. 5a-b, which depict the slope of the response forsensor 304 as a function of flow rate.

Example 2

[0075] Referring to FIG. 6, an array 600 of eight nominally identicalpoly(ethylene-co-vinylacetate)-carbon black composite sensors 601-608was prepared in a row on a single ceramic substrate as described above.An aluminum plate 610 was placed over the substrate, separated from thesubstrate surface by narrow Teflon spacers to create a small channelapproximately 5 mm wide and 70 microns high over the row of sensors,with openings 615, 620 at either end. The substrate assembly was placedin a Teflon chamber 630 of dimensions approximately 5 cm by 5 cm by 10cm. A stream of air was directed through the Teflon chamber. Flows werecontrolled as described in Severin, E. J., Doleman, B. J., Lewis, N. S.,Anal. Chem., 2000, 72, 658. During times of exposure, this stream alsocontained one of the four analytes at 5% of its vapor pressure. Fouranalytes covering a range of vapor pressures were used to study theresponse characteristics: n-dodecane, n-nonane, methanol, and n-hexane.The total flow into the chamber was maintained constant at all times.

[0076] The ΔR/R response was calculated using data averaged over fivesecond periods. The baseline resistance, R, was taken from the periodimmediately before starting the vapor presentation and the value of ΔR/Rwas taken as the difference in resistance after 300 seconds of vaporpresentation and the baseline resistance. This response was calculatedfor each of the eight sensor positions.

[0077] The spatial dependence of sensor responses to these analytes ateach of the eight sensors is shown in FIG. 7. The high vapor pressureanalytes produced equilibrium responses of similar magnitude on all ofthe sensors. By contrast, the lower vapor pressure analytes (n-nonaneand n-dodecane) produced higher magnitude responses on the sensors nearthe openings than on the sensors in the middle of the channel.

Example 3

[0078] An array 300 of eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black composite sensors 301-308 wasconstructed as described above and configured as described in Example 1.

[0079] The experimental protocol consisted of one hour of exposure toair only, followed by ten control exposures to 5 s DNT pulses spacedevery 605 s, followed by a randomized sequence of 20exposures/nonexposures to DNT spaced every 605 s. The data were thenanalyzed independently without knowledge of the actual order of therandomized sequence of exposures/nonexposures.

[0080] A run was also performed to investigate whether responses wouldbe obtained due to small changes in the flow rate of gas to the sensors.For this experiment, the existing lines were unhooked at the outlets ofboth mass flow controllers (the one feeding the DNT generator and theone providing diluent air). The lines were then replaced with lines anda union-T that had never been exposed to DNT or to solvents. The lengthsof the flow paths with the new lines in place approximated those in theDNT dilution system. A run of four 60 s exposures, each separated by 10min, was performed. In this run, 5% of the air during each exposure camevia the mass flow controller that was normally used to feed the DNTgenerator. The total flow rate at all times was 10 L-min⁻¹.

[0081]FIG. 8 shows the resistance (in units of 10 kΩ) versus timeprofile computed by averaging over the bank of eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black sensors that were placedperpendicular to the outlet of the DNT flow. The vertical lines show theground truth of when the DNT puffs were applied. The first ten linesrepresent the control set. Note that the time axis spans over 6 hours(22,000 s). The series of “bumps” that are visible on this long timescale plot are not related to the DNT pulses, and in fact representenvironmentally-induced oscillations in the baseline resistance of thesensor. The DNT-induced behavior occurs on a 5 second time scale that isnot discernible on this plot.

[0082]FIG. 9 plots sensor output versus time over the 6+ hours of theexperiment. The vertical lines show the ground truth of when DNT puffswere applied. The units on the y-axis are in standard deviations of thesignal relative to the local background of the sensor. As shown in FIG.9, using essentially a matched filter algorithm with adaptive backgroundsubtraction, all DNT exposures and non-exposures were correctlyidentified within the randomized sequence. The black circles show localmaxima of the sensor output that exceeded a given threshold. Based onthis selection criterion, all of the DNT exposures were detected with nofalse alarms. In fact, a much stronger result was obtained: theseparability at the sensor output was sufficient for all DNT exposures(in the control set and the randomized set) to be correctly identifiedwith zero false alarms over the entire >6 hour duration of theexperiment.

[0083] The highest sensor output value (15.3) occurred at the 6thcontrol sample. The resistance versus time profile for this sample isshown in detail in FIG. 10a. The sensor output versus time is shown inFIG. 10b. An intermediate case (roughly the median in sensor outputfidelity) occurred at the 4th control sample. The resistance versus timeprofile for this sample is shown in detail in FIG. 11a. The sensoroutput versus time is shown in FIG. 11b. The lowest sensor output value(7.35) occurred at the 7th control sample. The resistance versus timeprofile for this sample is shown in detail in FIG. 12a. The sensoroutput versus time is shown in FIG. 12b.

[0084] Although all the DNT exposures were perfectly separated from thebackground with zero false alarms, it is interesting to look at the“close calls” or “near false alarms”. In FIG. 9 there are 4 places wherethe sensor output on the background exceeds a threshold of 5 but isstill well below the minimum target value of 7.35. The detailedresistance versus time profiles for 2 of these 4 “near false alarms” areshown in FIGS. 13a-b.

Example 4

[0085] A separate set of experiments was performed to evaluate thedependence of DNT detection on the flow rate of DNT to the sensors. Forthis run, a poly(methyloctadecylsiloxane)-carbon black mixture wasspray-coated onto the edges of glass slides. Prior to the deposition ofthe sensor film, conductive coatings had been deposited onto bothsurfaces of the slides. Spacers were then placed between theseedge-coated slides. The result was a sensor with a width of ≈6 mm thathad slits 0.13-0.25 mm in width spanning the length of the sensor. Thisventilated sensor assembly was then cemented into one end of a sectionof vacuum hose. The other end of the hose was connected to a vacuumpump. A flow meter was placed in the line to monitor the flow ratethrough the slits in the sensor. The rectangular sensor face was fittedinto a similarly-sized aperture in a Teflon block, the fit being looseenough that gas flow onto the sensor could escape around the edges. Theoutput tube of the gas mixer was fitted to a second teflon block thatwas bolted to the block holding the sensor assembly, creating a smallchamber with a volume of about 0.3 cm³. The resulting distance betweenthe gas mixture outlet and the sensor was 5 mm. The resistance of thesensor was measured by connecting the leads to one channel in a dataacquisition board that recorded the resistance versus time data. Thedata were then transferred to a laptop computer.

[0086] Four trials were performed, with each trial using vapor emergingfrom the DNT-containing analyte tube diluted to 5% by volume withbackground air. In experiment 1, 10 exposures were made following a 20min purge with air at 10 L-min⁻¹. Each DNT exposure was 10 s in length.The total flow rates into the sensor chamber were varied progressively,starting at 1 L-min⁻¹ for the first exposure and ending with an exposureat 10 L-min. Each exposure was followed by a purge at 10 L-min⁻¹ ofbackground air. Prior to each exposure, the flow through the vacuum linedrawing gas through the sensor was set to produce a flow rate that was 1L-min⁻¹ less than the flow rate impinging onto the sensor chamber. Thispositive differential flow rate arrangement was used to avoid drawing inambient air through the remaining gap between the sensor and the wallsof the chamber.

[0087] In experiment 2, 10 exposures were made using the same ascendingseries of total flow rates into the chamber (i.e. 1-10 L-min⁻¹), but novacuum was applied during any of the exposures.

[0088] In experiment 3, the same ascending series of flow rates into thechamber was used, and the same ascending series of vacuum-induced flowrates through the sensor as in experiment 1 was employed, but no analyte(DNT) was present.

[0089] In experiment 4, the flow rate of DNT (at 5% of its vaporpressure at 20° C.) into the chamber as not varied, being maintained at10 L-min⁻¹ for all 10 exposures. Vacuum-induced flow rates through thesensor were, however, varied in the same way as in experiments 1 and 3,beginning with no flow for the first exposure and ending with 9 L-min⁻¹during the 10^(th) and final exposure.

[0090]FIG. 14a-b illustrates the dependence of signal from theventilated sensor on flow rate with the flow rate varying from 1 to 10liters/min. FIG. 14a shows resistance transients for a 1 minute exposureof DNT at 5% of its vapor pressure (top: vacuum on; bottom: vacuum off).FIG. 14b shows the change in resistance as a function of time indicatingmagnitude of slope during exposure. As these figures illustrate, pullinganalyte through the sensor at a rate about 1 L-min⁻¹ less than the flowrate of gas into the chamber generally resulted in an increase in sensorresponse of a factor of 2. This was particularly noticeable at higherflow rates. When flow into the sensor chamber was kept at a constant,high rate (10 L-min⁻¹) , the sensor response increased, apparently dueto increased flow through the sensor slits.

[0091] The ventilated sensor response characteristics for 5 s exposuresto 10 L-min⁻¹ total flow rates of 5% DNT as a function of flow ratethrough the sensor are illustrated in FIGS. 15a-c. FIG. 15a showsresponse transients ranging from no flow through the sensor (second fromthe bottom) to 9 L-min⁻¹ through the sensor (top). FIG. 15b showsresponse slope as a function of flow rate through the sensor. FIG. 15cshows signal to noise after 5 s exposure as a function of flow rate.

[0092] Although only a few embodiments have been described in detailabove, those having ordinary skill in the art will certainly understandthat many modifications are possible in the preferred embodiment withoutdeparting from the teachings thereof. All such modifications areintended to be encompassed within the following claims.

What is claimed is:
 1. A system for detecting an analyte in a fluid,comprising: a sensor array including at least a first sensor and asecond sensor in an arrangement having a defined fluid flow path; ameasuring apparatus coupled to the sensor array, the measuring apparatusbeing configured to detect a response from the first sensor and thesecond sensor upon exposure of the sensor array to a fluid; and acomputer configured to generate data indicating the presence of theanalyte in the fluid based on a spatio-temporal difference between theresponses for the first and second sensors.
 2. The system of claim 1,wherein: the data indicating the presence of the analyte in the fluidincludes a spatio-temporal response profile derived from thespatio-temporal difference between the responses for the first andsecond sensors.
 3. The system of claim 2, wherein: the spatio-temporalresponse profile is derived from time information indicating thedependence of sensor response on time.
 4. The system of claim 3,wherein: the first sensor occupies a first position in the arrangementand the second sensor occupies a second position in the arrangement,such that the response of the second sensor is delayed in time withrespect to the response of the first sensor upon exposure of the sensorarray to the fluid.
 5. The system of claim 3, wherein: the first sensoroccupies a first position in the arrangement and the second sensoroccupies a second position in the arrangement, such that the response ofthe second sensor is changed in amplitude with respect to the responseof the first sensor upon exposure of the sensor array to the fluid. 6.The system of claim 5, wherein: the first sensor includes a sensingmaterial; and the response of the first sensor is greater than theresponse of the second sensor for an analyte having a high affinity forthe sensing material.
 7. The system of claim 4, wherein: the first andsecond sensors are selected and arranged to provide a first delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a firstanalyte and a second delay between the response of the first sensor andthe response of the second sensor upon exposure of the sensor array to afluid including a second analyte.
 8. The system of claim 7, wherein: themeasuring apparatus is configured to measure the delay between theresponse of the first sensor and the response of the second sensor; andthe spatio-temporal difference between the responses for the first andsecond sensors is derived from the delay.
 9. The system of claim 8,wherein: the computer is configured to characterize the analyte based onthe spatio-temporal difference between the responses.
 10. The system ofclaim 2, further comprising: a flow controller to introduce the fluid tothe sensor array at a varying flow rate.
 11. The system of claim 10wherein: the computer is configured to generate flow informationindicating the dependence of sensor response on flow rate.
 12. Thesystem of claim 2, wherein: the sensor array includes a plurality ofcross-reactive sensors.
 13. The system of claim 2, wherein: the sensorarray includes a plurality of sensors selected from the group includingsurface acoustic wave sensors, quartz crystal resonators, metal oxidesensors, dye-coated fiber optic sensors, dye-impregnated bead arrays,micromachined cantilever arrays, composites having regions of conductingmaterial and regions of insulating organic material, composites havingregions of conducting material and regions of conducting orsemiconducting organic material, chemically-sensitive resistor orcapacitor films, metal-oxide-semiconductor field effect transistors, andbulk organic conducting polymeric sensors.
 14. The system of claim 2,wherein: the first and second sensors comprise composites having regionsof a conducting material and regions of an insulating organic material.15. The system of claim 2, wherein: the first and second sensorscomprise composites having regions of a conducting material and regionsof a conducting organic material.
 16. The system of claim 2, wherein:the computer is configured to generate a digital representation of theanalyte based at least in part on the responses of the first and secondsensors.
 17. The system of claim 16, further comprising: acommunications port coupled to the computer for communicating thedigital representation of the analyte to a remote location for analysis.18. A system for detecting an analyte in a fluid, comprising: a sensorarray including a first sensor and a second sensor; a fluid inletproximate to the sensor array, the fluid inlet defining a fluid flowpattern for the introduction of a fluid onto the sensor array, such thatthe first and second sensors are located at different locations in thesensor array relative to the fluid flow pattern; and a measuringapparatus connected to the sensor array, the measuring apparatus beingconfigured to detect a response from the first sensor and the secondsensor upon exposure of the sensor array to a fluid, the responsesdefining a spatio-temporal difference between the responses for thefirst and second sensors based on the locations of the sensors relativeto the fluid flow pattern.
 19. The system of claim 18, wherein: thespatio-temporal difference is derived from time information indicatingthe dependence of sensor response on time.
 20. The system of claim 19,wherein: the first sensor occupies a first position relative to thefluid flow pattern and the second sensor occupies a second positionrelative to the fluid flow pattern, such that the response of the secondsensor is delayed with respect to the response of the first sensor uponexposure of the sensor array to the fluid.
 21. The system of claim 19,wherein: the first sensor occupies a first position relative to thefluid flow pattern and the second sensor occupies a second positionrelative to the fluid flow pattern, such that the response of the secondsensor is changed in amplitude with respect to the response of the firstsensor upon exposure of the sensor array to the fluid.
 22. The system ofclaim 21, wherein: the first sensor includes a sensing material; and theresponse of the first sensor is greater than the response of the secondsensor for an analyte having a high affinity for the sensing material.23. The system of claim 20, wherein: the first and second sensors areselected and arranged to provide a first delay between the response ofthe first sensor and the response of the second sensor upon exposure ofthe sensor array to a fluid including a first analyte and a second delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a secondanalyte.
 24. The system of claim 23, wherein: the measuring apparatus isconfigured to measure the delay between the response of the first sensorand the response of the second sensor; and the spatio-temporaldifference between the responses for the first and second sensors isderived from the delay.
 25. The system of claim 19, further comprising:a computer configured to characterize the analyte based on thespatio-temporal difference between the responses.
 26. The system ofclaim 18, further comprising: a flow controller to introduce the fluidto the sensor array at a varying flow rate.
 27. The system of claim 26,wherein: the measuring apparatus is configured to measure flowinformation indicating the dependence of sensor response on flow rate.28. The system of claim 18, wherein: the sensor array includes aplurality of cross-reactive sensors.
 29. The system of claim 18,wherein: the sensor array includes a plurality of sensors selected fromthe group including surface acoustic wave sensors, quartz crystalresonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors.
 30. Thesystem of claim 18, wherein: the first and second sensors comprisecomposites having regions of a conducting material and regions of aninsulating organic material.
 31. The system of claim 18, wherein: thefirst and second sensors comprise composites having regions of aconducting material and regions of a conducting organic material. 32.The system of claim 25, wherein: the computer is configured to generatea digital representation of the analyte based at least in part on theresponses of the first and second sensors.
 33. A system for detecting ananalyte in a fluid, comprising: a sensor array including a first sensorand a second sensor; a fluid flow exposing the first and second sensorsto a fluid, such that the first and second sensors occupy differentlocations in the sensor array relative to the fluid flow; and ameasuring apparatus connected to the sensor array, the measuringapparatus being configured to detect a response from the first andsecond sensors upon exposure of the sensor array to the fluid flow, theresponses defining a spatio-temporal difference based on the locationsof the sensors in the sensor array relative to the fluid flow.
 34. Thesystem of claim 33, wherein: the spatio temporal difference is derivedfrom time information indicating the dependence of sensor response ontime.
 35. The system of claim 34, wherein: the first sensor occupies afirst position relative to the fluid flow and the second sensor occupiesa second position relative to the fluid flow, such that the response ofthe second sensor is delayed with respect to the response of the firstsensor upon exposure of the sensor array to the fluid.
 36. The system ofclaim 34, wherein: the first sensor occupies a first position relativeto the fluid flow and the second sensor occupies a second positionrelative to the fluid flow, such that the response of the second sensoris changed in amplitude with respect to the response of the first sensorupon exposure of the sensor array to the fluid.
 37. The system of claim36, wherein: the first sensor includes a sensing material; and theresponse of the first sensor is greater than the response of the secondsensor for an analyte having a high affinity for the sensing material.38. The system of claim 35, wherein: the first and second sensors areselected and arranged to provide a first delay between the response ofthe first sensor and the response of the second sensor upon exposure ofthe sensor array to a fluid including a first analyte and a second delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a secondanalyte.
 39. The system of claim 38, wherein: the measuring apparatus isconfigured to measure the delay between the response of the first sensorand the response of the second sensor; and the spatio-temporaldifference between the responses for the first and second sensors isderived from the delay.
 40. The system of claim 33, further comprising:a computer configured to characterize the analyte based on thespatio-temporal difference between the responses.
 41. The system ofclaim 33, further comprising: a flow controller to vary the rate of thefluid flow.
 42. The system of claim 41, wherein: the measuring apparatusis configured to measure flow information indicating the dependence ofsensor response on flow rate.
 43. The system of claim 33, wherein: thesensor array includes a plurality of cross-reactive sensors.
 44. Thesystem of claim 33, wherein: the sensor array includes a plurality ofsensors selected from the group including surface acoustic wave sensors,quartz crystal resonators, metal oxide sensors, dye-coated fiber opticsensors, dye-impregnated bead arrays, micromachined cantilever arrays,composites having regions of conducting material and regions ofinsulating organic material, composites having regions of conductingmaterial and regions of conducting or semiconducting organic material,chemically-sensitive resistor or capacitor films,metal-oxide-semiconductor field effect transistors, and bulk organicconducting polymeric sensors.
 45. The system of claim 33, wherein: thefirst and second sensors comprise composites having regions of aconducting material and regions of an insulating organic material. 46.The system of claim 33, wherein: the first and second sensors comprisecomposites having regions of a conducting material and regions of aconducting organic material.
 47. The system of claim 40, wherein: thecomputer is configured to generate a digital representation of theanalyte based at least in part on the responses of the first and secondsensors.